Attention Deficit Hyperactivity Disorder (ADHD) is characterized by heterogeneous problems with inattention, impulsivity, and hyperactivity. Mercugliano, 1999, Pediatr. Clin. North Am. 46:831-843; Faraone, et al., 1999, “The neurobiology of attention deficit hyperactivity disorder” in Neurobiology of Mental Illness, Charney, et al., eds., Oxford University Press, New York, pp. 788-801. It is one of the most commonly diagnosed behavioral disorders in children, affecting approximately 3-5% of school age children Faraone, et al., 1999, supra; 1998, “Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder (ADHD)” NIH Consensus Statement 16:1-42. In addition, it is estimated that the majority of patients with ADHD will continue to have significant symptoms as adults. NIH Consensus Statement, supra. Adults with ADHD tend to have fewer problems with hyperactivity, but more problems with inattention and distractibility. Many patients have ADHD in conjunction with other psychiatric disorders (co-morbidities), including depression, anxiety, conduct disorders, oppositional disorder, obsessive compulsive disorder, and alcohol and/or substance abuse. Biederman, et al., 1993, Am. J. Psychiatry 150:1792-1798. The symptoms of inattention, impulsivity, and hyperactivity significantly interfere with school and job performance and social interactions affecting both peers and families. Faraone, et al., 1999, supra. ADHD is typically treated with stimulant medications, although there is considerable controversy regarding the long-term use of these medications in children. Mercugliano, 1999, supra; NIH Consensus Statement, supra; Spencer, et al., 1996, J. Am. Acad. Child Adolesc. Psychiatry 35:409-432 [see comments].
The diagnosis of ADHD has evolved over the past fifty years as the syndrome has become better characterized. Although the current diagnostic criteria described in Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) are generally accepted, the validity of the diagnosis in many children and adults has been questioned because the diagnosis is based on subjective clinical evaluations. Spencer, et al., 1994, Harv. Rev. Psychiatry 1:326-335. A reliable diagnosis of ADHD can be made by expert psychiatrists or psychologists using standardized structured interviews and neuro-psychiatric tests to adequately assess the patient and rule out confounding co-morbidities. However, the diagnosis may be less reliable when made by inadequately trained or inexperienced practitioners. In addition, it is estimated that at least 40% of adult patients with a probable diagnosis of ADHD do not meet strict DSM-IV criteria, largely because of the criterion that symptoms begin before seven years of age. Applegate, et al., 1997, J. Am. Acad. Child Adolesc. Psychiatry 36:1211-1221; Barkley, et al., 1997, J. Am. Acad. Child Adolesc. Psychiatry 36:1204-1210 [see comments]. Thus, it appears that the clinical diagnosis of ADHD results in both the over- and under-diagnosis of large numbers of patients. An independent and objective biological test to support the clinical diagnosis of ADHD would be beneficial. NIH Consensus Statement, supra. However, there has been doubt expressed by physicians that structural imaging studies, e.g., using single photon emission tomography (SPECT), would prove to be useful for the evaluation or management of ADHD. Zametkin, et al., 1998, J. Clin. Psychiatry 59 (suppl. 7): 17-23.
Attention deficit-hyperactivity disorder (ADHD) is a recognized syndrome characterized by a relatively high incidence in children with persistence into adulthood. Some research suggests that ADHD has a genetic component. Biederman et al., 1995, Am. J. Psychiatry 152(3):431-35; Arnold et al., 1997, Arch. Gen. Psychiatry 54:865-70. Paradoxically, stimulant drugs such as methylphenidate, d-amphetamine and pemoline are effective medications for treating ADHD in children and adults. Seeman and Madras, 1998, Molecular Psychiatry 3:385-96; Arnold et al., 1997, supra; Greenhill, et al., 1999, J. Am. Acad. Child Adolesc. Psychiatry, 38(5):503-12; Wilens, et al., 1992, Psychiatric Clinics of N. Am. 15(1): 191-222.
Increased recognition of the disorder has led to increased prescription of stimulant medications for treating ADHD. There is concern about the possibility of over-diagnosis of ADHD and resulting unnecessary treatment with stimulant drugs that have inherent potential for abuse. Conversely, if ADHD is underdiagnosed, patients who could be helped may go untreated. Thus, improved methods and products for diagnosis of ADHD and assessment of the effect of treatment of ADHD are desired.